Injection halves risk of chromosome error common in older human eggs

Abnormal numbers of chromosomes in human eggs can result in miscarriage, IVF failure, and disorders like Down’s syndrome. Researchers have now discovered that a single injection into the eggs can significantly alleviate this issue, potentially increasing the success rate of IVF, particularly for older women.

“It really seems like a big deal,” comments Marcos Iuri Roos Kulmann from Nilo Frantz Reproductive Medicine in Porto Alegre, Brazil, who was not involved in the study. “To my knowledge, this is the first [therapy] to show such clinical potential for correcting this major cause of IVF failure.”

In meiosis, egg and sperm cells expel exactly half of their genetic material, so when they merge during fertilization, they create an embryo with a full genome. However, sometimes these cells have an incorrect number of chromosomes, a condition called aneuploidy.

Aneuploidy impacts approximately 10 to 25 percent of eggs in women in their early 30s, with the condition becoming more prevalent as women age. “Already in the late 30s, more than 65 percent of all eggs are aneuploid,” explains Agata Zielinska from Ovo Labs, a biotechnology firm in Germany, during the European Society of Human Reproduction and Embryology conference in London on July 6.

While clinicians sometimes check IVF embryos for aneuploidy for couples at high risk, for most, disorders due to genetic errors, such as Down’s syndrome, are only identified through blood tests and ultrasounds during the first trimester of pregnancy. Zielinska notes that until now, there were no methods to prevent aneuploidy from occurring initially.

Research by Zielinska and her team has found that the protein shugoshin-1 is significantly lower in older mouse and human eggs compared to younger ones. This protein plays a crucial role in meiosis by aligning chromosome pairs in immature egg cells and maintaining the cohesion between them.

During fertilization, chromosomes separate and move to opposite sides of the cell, with one end becoming the mature egg and the other being discarded. In older eggs, the degradation of the cohesion can cause premature chromosome separation, resulting in an uneven chromosome distribution and a higher risk of aneuploidy.

To test if increasing shugoshin-1 levels could prevent aneuploidy, the team gathered 111 immature eggs from over 30 women aged 22 to 43. They injected the genetic code for shugoshin-1 into some of the eggs, leaving others untreated.

After a few hours, premature chromosome separation occurred in 53 percent of untreated eggs compared to 29 percent of treated ones. In eggs from nine donors aged over 35, untreated eggs had an average aneuploidy rate of 65 percent, while treated eggs showed a 44 percent rate. Although this reduction was not statistically significant, researchers attribute this to the study’s small sample size.

Further experiments demonstrated that this method could prevent aneuploidy in mouse eggs, which were then successfully fertilized to produce healthy offspring. No side effects were noted in either mouse or human studies. “We’ve achieved live births in mice, so, from that perspective, we’re confident that this approach is not interfering in the mouse model with any steps of embryo development, and it doesn’t interfere with pup health and pregnancy health,” Zielinska informed the conference attendees.

The researchers aim to test shugoshin-1’s effects on humans, which would require minor adjustments to standard IVF practices to use immature rather than mature eggs, a change Zielinska believes would be straightforward to implement.

The team, referring to the treatment as EmbryoProtect, hopes it will offer an economical improvement to IVF for older women. “We anticipate that the treatment will cost a fraction of the cost of a full IVF cycle,” Zielinska states. “By meaningfully improving IVF success rates, especially for women over 35 where baseline success is low, we hope that fewer attempts will be needed to conceive.”